Allergy is a phenomenon in which a living body in contact with an exogenous substance exhibits a response to the substance different from normal responses. When an organism comes into contact with an exogenous substance, an antigen-antibody reaction causes an abrupt change in the body's ability to respond thereto, which is called allergy. For a heterologous substance, the living organism produces antibodies and lymphocytes that specifically react with the antigen, and when the living organism comes into contact the antigen again, it causes various immune responses. This immune response or immune reaction is one of the important defense mechanisms for self-preservation of the living body, and usually acts protectively on the living body, but sometimes this mechanism adversely acts on the living body, thus causing disorders. Allergy means “hypersensitive,” and is derived from a Greek word allos, which means “altered.” The term “allergy” was first used by the French scholar von Pirque in 1906. Allergy is pronounced in English as al-ler-gi or el-ler-gi and in German as al-le-r-gie, and both are interchangeably used in Korea. Antigens that cause allergic reactions are called allergens, and typical allergens include pollen, drugs, plant fibers, bacteria, food, dyes, chemicals, and the like. The immune system has several defense mechanisms to protect the body against antigens. The most common type of these mechanisms is lymphocytes, which are specified to be in response to specific antigens and include B cells and T cells. B cells bind to an antigen to produce an antibody, which is a protein that destroys and neutralizes the antigen. T cells directly bind to an antigen to thereby stimulate attack, instead of producing an antibody. An allergic reaction occurs as immediate allergy or delayered allergy, and is determined depending on with which of B cells and T cells an antigen reacts. As diseases caused by allergy, there are various diseases including autoimmune diseases, collagen diseases, and the lie, and allergic diseases generally include classical allergic diseases such as anaphylactic shock, food allergy, allergic rhinitis, pollinosis, bronchial asthma, drug allergies, plant allergies, urticaria, eczema, and allergic contact dermatitis. These are allergy-caused diseases, but there are cases in which other in vivo conditions are required for their onset. In addition, same symptoms may be caused by non-allergic mechanisms.
Atopic dermatitis is a chronic, highly recurrent inflammatory skin disease that starts mainly in infancy or childhood, and is accompanied by pruritus (itching), dry skin, and characteristic eczema. In infancy, it starts with eczema on the face and the unfolded parts of the limbs, but characteristically appears as eczema on the bent parts of the arms and the bent parts of back sides of the knees as infants grow. In many cases, atopic dermatitis tends to alleviate naturally as children grow. In adults, lichenification, which is a condition of thickening of the folded skin parts, appears, and many adult cases show eczema on the face, unlike those in childhood. Atopic dermatitis tends to increase globally and the prevalence rate has been reported as 20% of the population.
Despite advanced allergic treatment for allergic patients and a growing increase in sales of excellent allergy therapeutic agents, allergic symptoms of people have become severe and the number of allergic patients is increasing rapidly.
These are attributable to limitations of existing therapeutic agents including the amplification of allergic diseases via various other routes, temporary improvement effects, and the like.
Existing atopic dermatitis therapeutic agents alleviate pruritus and restore damaged skin surface, and are mostly immunosuppressants or steroid agents which are recognized to have side effects.
Therefore, there is a need to develop a therapeutic agent capable of treating atopy as immune hypersensitivity by addressing fundamental causes of atopy in atopy treatment, unlike immunosuppressants or steroid agents which have previously been reported to have side effects.
Meanwhile, inflammatory bowel disease (IBD) is classified into two diseases: ulcerative colitis and Crohn's disease, which are clinically similar but different from each other in histological, endoscopic, and immunological aspects, and the activation of inflammatory cells is known to be an important etiology of IBD. Continuous or improper activation of the intestinal immune system plays an important role in the pathophysiology of chronic mucosal inflammation, and in particular, the infiltration of neutrophils, macrophages, lymphocytes, and mast cells eventually results in mucosal destruction and ulceration. Infiltered and activated neutrophils lead to generation of reactive oxygen species and reactive nitrogen species, and these active species are cytotoxic substances that induce cellular oxidative stress by crosslinked proteins, lipids, and nucleic acids and cause epithelial dysfunction and damage.
When an inflammatory disease occurs, a variety of inflammatory cytokines are secreted in the mucosa of the intestinal tract. TNF-α is highly expressed in colonic lumens and colonic epithelial cells in patients with ulcerative colitis. According to recent studies, it has been known that TNF-α plays an important role in the pathogenesis of ulcerative colitis. Infliximab, which is an anti-TNF-α antibody, has been known to be effective not only in the treatment of boils, but also in the treatment of previously untreated Crohn's disease. However, such therapies are costly and, in some patients, cause side effects such as fluid responses or infectious complications.
Currently, 5-aminosalicylic acid (5-ASA)-based drugs that block the production of prostaglandins, for example, sulfasalazine and the like, or immunosuppresants such as steroids are used as therapeutic agents for inflammatory bowel disease.
Sulfasalazine is prone to cause side effects or adverse effects such as abdominal fullness, headache, rash, liver disease, leukopenia, agranulocytosis, male infertility, and the like. In addition, it is unclear whether sulfasalazine has a sufficient effect of inhibiting recurrence in patients with the affected part of the intestine incised or patients showing improvement.
Steroid immunosuppressants are adrenocortical steroids, which may show short-term effects but cannot improve the long-term prognosis and have limitations in being used only in acute cases due to side effects such as induced infectious diseases, secondary adrenocortical insufficiency, peptic ulcer, diabetes, mental disorder, and steroid kidney disease.
Thus, there have not yet been reliable therapeutics for inflammatory bowel disease, and therefore, there is a need to develop an effective therapeutic agent therefor.